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The phenotypic and functional identification of angiogenic T-cells for potential use to treat cardiovascular disease Project ID SAS0043


Project Description

PROJECT DESCRIPTION
This project is based within the School of Applied Sciences at Edinburgh Napier University and is led by Dr. Mark Ross (https://www.napier.ac.uk/people/mark-ross), Dr. Graham Wright (https://www.napier.ac.uk/people/graham-wright), and Professor Nicholas Mills (https://www.research.ed.ac.uk/portal/en/persons/nicholas-mills), and is investigating the use of T-cells to stimulate angiogenesis to promote vascular health, and to treat cardiovascular disease.

Cardiovascular disease (CVD) is the most common cause of death in western civilisation (WHO, 2014). A significant proportion of this mortality is attributable to recurring cardiac events post initial myocardial infarction (Jernberg et al., 2015) due to insufficient repair and regeneration of the vasculature supplying the heart with new blood vessels (angiogenesis) to aid tissue repair.

Circulating ‘angiogenic’ cells (CAC) are a subset of circulating cells in our bloodstream that play a very important role in promoting blood vessel repair, regeneration, and reducing cardiovascular disease (CVD) risk. One such subset of CACs, termed ‘angiogenic’ T-cells, are a group of lymphocytes (subset of our white blood cells) which, in addition to their crucial role in controlling immune responses, are also potent potentiators of vascular growth and repair (Hur et al., 2007; Kushner et al., 2010). Limited functional studies have demonstrated that angiogenic T cells can stimulate the cells lining our blood vessels (endothelial cells) to proliferate and repair by secreting soluble factors, however, the other roles of these T cells have not been defined, including their cross-over with immune function.

One area with huge potential for future therapy is the use of pro-angiogenic cells to improve collateral artery formation in peripheral arterial disease patients, and instigate vascular repair in heart attack patients. Currently, another subset of CACs, called endothelial progenitor cells (EPCs) are being applied as an experimental therapy in heart failure and cardiovascular disease patients. However, despite the clinical promise of EPCs their therapeutic potential is limited by their paucity in the peripheral circulation (0.0001-0.0010% of total peripheral blood mononuclear cells). In contrast T-cells are the predominant peripheral blood leukocyte (representing 15-45%) and are currently being successful explored as a cell therapy in cancer. As such, T-cells may be well placed to offer therapeutic angiogenesis treatments. In order for a T cell therapy for cardiovascular disease to be realised a full understanding of the angiogenic potential and functions of the different subsets needs to be established.

The aim of this PhD is to define the phenotype of T-cells with maximal angiogenic potential. Furthermore, to validate the potential of this population we will correlate the defined populations with cardiovascular recovery in myocardial infarction patients. This study has been designed to lay the foundation to future clinical application of angiogenic T cell therapy for CVD.

You will be given the opportunity to engage in active postgraduate research group. You will be provided extensive training in imaging, biological sampling, flow cytometry and confocal microscopy. You will be given the opportunity to engage with an active post-graduate research community (including the chance to present at national/international conferences) and take part in a full training programme aimed at supportuning progression to a successful research career.

Academic qualifications
A first degree (at least a 2.1) ideally in Biomedical Science or Immunology with a good fundamental knowledge of cardiovascular and immunological physiology.

English language requirement
IELTS score must be at least 6.5 (with not less than 6.0 in each of the four components). Other, equivalent qualifications will be accepted. Full details of the University’s policy are available online.

Essential attributes:
• Experience of fundamental biological laboratory skills
• Competent in statistics
• Knowledge of cardiovascular physiology and immunology
• Good written and oral communication skills
• Strong motivation, with evidence of independent research skills relevant to the project
• Good time management

Desirable attributes:
Prior experience of tissue culture, flow cytometry and immunoassays

WHEN APPPLYING FOR THIS POSITION PLEASE QUOTE PROJECT CODE - SAS0043

Funding Notes

SELF FUNDED POSITION

APPLICATION CHECKLIST
-Completed application form
-CV
-2 academic references, using the Postgraduate Educational Reference Form (Found on the application process page)
-A personal research statement (This should include (a) a brief description of your relevant experience and skills, (b) an indication of what you would uniquely bring to the project and (c) a statement of how this project fits with your future direction. If you are not responding to an advertised project, then your personal research statement will need to include an outline of the project you are proposing)
-Evidence of proficiency in English (if appropriate)

References

HUR, J., YANG, H. M., YOON, C. H., LEE, C. S., PARK, K. W., KIM, J. H., KIM, T. Y.,
KIM, J. Y., KANG, H. J., CHAE, I. H., OH, B. H., PARK, Y. B. & KIM, H. S. 2007.
Identification of a novel role of T cells in postnatal vasculogenesis: characterization of endothelial progenitor cell colonies. Circulation, 116, 1671- 82.

KUSHNER, E. J., MACENEANEY, O. J., MORGAN, R. G., VAN ENGELENBURG, A. M., VAN GUILDER, G. P. & DESOUZA, C. A. 2010. CD31+ T cells represent a
functionally distinct vascular T cell phenotype. Blood Cells Mol Dis, 44, 74-8.

ROSS, M. D., MALONE, E. M., SIMPSON, R., CRANSTON, I., INGRAM, L., WRIGHT, G.
P., CHAMBERS, G. & FLORIDA-JAMES, G. 2018. Lower resting and exercise- induced circulating angiogenic progenitors and angiogenic T cells in older men. Am J Physiol Heart Circ Physiol, 314, H392-H402.


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